Abstract

Background

Endotoxins are ubiquitously present in the environment and constitute a significant
component of ambient air. These substances have been shown to modulate the allergic
response, however a consensus has yet to be reached whether they attenuate or exacerbate
asthmatic responses. The current investigation examined whether reducing the concentration
of lipopolysaccharide (LPS) in a house dust extract (HDE) containing high concentrations
of both cockroach allergens [1] and LPS would attenuate asthma-like pulmonary inflammation.

Methods

Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng
of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA.
Multiple parameters of asthma-like pulmonary inflammation were measured.

Results

Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly
reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and
IgG1 were significantly reduced, however no change in CRA-specific IgE was detected.
In HDE mice, plasma IgG2a levels were similar to naïve mice, while LPS-reduced HDE
mice had significantly greater concentrations. Reduced levels of LPS in the HDE did
not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent
inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations
of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge
induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL
fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine
challenge. Conclusion: These data show that reduction of LPS levels in the HDE does not significantly protect
against the severity of asthma-like pulmonary inflammation.